Bristol Myers Squibb Discloses Patient Death in Multiple Sclerosis CAR-T Trial, Targets Early 2027 Restart

Bristol Myers Squibb (BMS) has confirmed that a patient died in its phase 1 trial of the CAR-T therapy zolacabtagene autoleucel, known as zola-cel, in multiple sclerosis. The company disclosed the death on Friday, Oct. 23, alongside interim data presented at MSToronto2026, the joint ECTRIMS and ACTRIMS meeting.

The patient died of septic pneumonia 44 days after receiving the infusion. BMS says no other deaths have occurred among the 190 patients treated with zola-cel in autoimmune studies.

What happened to the patient

Jeffrey Cohen, MD, of the Cleveland Clinic Mellen Center, presented the case. The patient had highly active relapsing MS.

On day 17 after infusion, the patient developed extrapyramidal motor symptoms, including rigidity and tremor. Doctors treated them with intermittent corticosteroids and intravenous immunoglobulin. The symptoms did not resolve.

On day 41, with no alternative cause identified, the patient received high-dose cyclophosphamide to target circulating CAR-T cells. Cyclophosphamide was part of the original treatment protocol and was used again in this case. Septic pneumonia developed on day 43. The patient died on day 44, the day after the cyclophosphamide was administered.

The death occurred after the study's June 2026 data cutoff. "The pathogenesis of that event is not fully understood," Cohen said. He added that the event is still being investigated. Cell expansion in this patient was in line with the other participants, he noted.

BMS was explicit about the limits of what it can conclude. "The motor symptoms were a late-onset side effect, and the patient had a series of other complications and was heavily pretreated prior to CAR T, confounding our ability to determine the root cause of the issue or draw further conclusions," the company said.

BMS says the death is separate from the pause

BMS paused enrollment in its autoimmune zola-cel trials in late August, citing what it called "transient and reversible inflammatory events." Pharma Executive and MedPage Today place the pause in September; Fierce Biotech and Endpoints News describe it as a summer or August pause.

Lynelle Hoch, president of BMS's cell therapy organization, told Fierce Biotech that the patient received zola-cel before the pause and died "well after the pause." She said the death was "not related to our pause in any way, because this patient's toxicities was not even a signal and related to the ICANs and why we paused the trial." ICANS, immune effector cell-associated neurotoxicity syndrome, is a known neurological side effect of CAR-T therapy. BMS described the patient's symptoms as "late-onset, non-ICANS motor symptoms."

Hoch also told Fierce that the company has "found the root cause for the trend break that we saw" and is "eager to return zola-cel to clinical trials with our previous process."

The pause came during a summer in which Novartis also halted development of its autologous CD19 CAR-T therapy, rapcabtagene autoleucel, for several autoimmune diseases after three deaths from complications of serious immune effector cell-associated hemophagocytic syndrome. Pharma Executive reports that Novartis halted eight clinical trials of its experimental cell therapy. MedPage Today describes the Novartis deaths differently, as ICANS-related.

An independent data monitoring committee reviewed the fatal event and determined that the MS cohorts may proceed once the Breakfree program restarts.

The Breakfree-2 numbers

Breakfree-2 enrolled 66 MS patients: 30 with highly active relapsing disease and 36 with progressive disease, who had ongoing disease activity or worsening disability despite a median of two prior disease-modifying therapies. Safety was the primary endpoint. Efficacy was secondary.

• Cytokine release syndrome occurred in 42.4% of patients (28 of 66). BMS says 36.4% had Grade 1 and 6.1% Grade 2, and all resolved in a median of two days.
• ICANS occurred in 7.6% (5 of 66), mostly Grade 1 or 2. One Grade 4 case in a progressive MS patient resolved within four days after treatment with corticosteroids and anakinra.
• All 60 patients treated at dose level 2 remained off disease-modifying therapies at last follow-up, including nine followed for more than 12 months.
• Among evaluable dose level 2 patients with at least 26 weeks of follow-up, six of seven with relapsing MS met criteria for no evidence of disease activity. Twenty-two of 24 with progressive MS showed stability or improvement in disability despite prior worsening.

Cohen cautioned that the trials are small with relatively short follow-up and are for the most part uncontrolled and open-label, so efficacy results have to be interpreted with caution.

The company's case and the open concern

BMS frames the data as encouraging. "The Breakfree-2 data demonstrate clinical potential for zola-cel in multiple sclerosis, showcasing the opportunity for treatment-free remission in patients who have depended on chronic therapies for years," Hoch said. She also told Fierce, "Of course, the Grade 5 event that happened weighs heavily on our hearts."

Cohen said the data suggest CD19-directed CAR-T may offer a new approach to MS. "While more research is needed, the potential to control relapses, stabilize disability and reduce reliance on disease-modifying medications is encouraging," he said.

Tech Times reports a hypothesis from William Blair analysts that rapid manufacturing, a feature shared by zola-cel and Novartis's rapcabtagene autoleucel, could drive increased cell expansion and the reported toxicities. That hypothesis has not been confirmed.

What comes next

BMS says it is working with the FDA to restart all zola-cel studies and aims to resume enrollment in early 2027. The company has not publicly said whether the FDA has agreed to a restart timeline.

The unresolved question is the cause of the extrapyramidal motor symptoms that began on day 17. BMS says it cannot determine the root cause, and Cohen described the mechanism as not fully understood. The answer will likely shape the restart and how quickly zola-cel can advance toward later-stage development in MS and other autoimmune diseases.